Part 6: Antiviral agents Flashcards
viruses use host cell ____ and ____ to reproduce
biochemica pathways and replication machinery
many viruses are catergorized into 2 groups ___
RNA and DNA viruses
Herpes simplex virus, and varicella zoster virus are examples of ____ type viruses
DNA
HIV, Hepatitis, Influenza, SARS-CoV2 are examples of ___ type viruses
RNA
what are reverse transcribing viruses?
RNA viruses that use an enzyme (reverse transcriptase) to create viral DNA that is integrated into the host genome prior to replication
what enzyme is used by reverse transcribing viruses
reverse transcriptase
give an example of a reverse transcribing virus
HIV
why is it so hard to target viruses with drugs?
because they are simplistic mOs that use host materials; and many of them mutate extensively
1st step for viral infection
viral attachment and entry into host cells
2nd step for viral infection
genetic material is released intto the cytoplasm (uncoating)
3rd step for viral infection
once all the componenets are in the cytoplasm, replication begins
replication process depends on the virus, but in general, there are a few viral and host ____ and ____ involved
enzymes and replication machinery
4th step in viral infection
new viral particles are packaged and released to infect other host cells
what happens to the host cel during viral infection?
functions become impaired and are often killed in the process
if the host cell is not destryed by the virus, it may express____ on its surface
viral proteins
what is the point of a host cell displaying viral proteins on its surface?
causes the immune system to recognize the virus and begin to kill any cells with the antigen
t/f the immune response to viruses can oftne cause significant damage to our host cells as well
true
vira; drugs that have been optimized for pharmacological treatment often involve targetting _____ or ____
the virus entering or exiting the host cells
some antiviral work by rying to increase the host ___
immune response
what are immunomodulators?
pharm agents that interact with cells of the immmune system to boost the responsiveness and promote recognition of foreign agents
____ are a more specific approach to prime the immune system and promote memory of an infectious agent to facilitate a larger scale immune response should the infection ever show up
vaccinations
give an example of a drug used to treat herpes simplex virus
acyclovir
give 2 examples of drugs used to treat hepatitis C
ribavirin, IF-A
give 3 examples of drugs used to treat HIV
maraviroc, emtricitabine etravirine
give an example of a drug used to treat influenza
oseltamavir
give 3 examples of drugs used to treate COVID
remdeivir, hydroxychloroquine, bamlanivimab
what do DNA viruses like HSV do once theyve entered a host cell?
use a combo of host and their own enzymes to replicate their DNA and create new particles
acyclovir is an antiviral drug that is a ____ analogue
guanosine nucleoside
acyclovir is similar enough to endogenous nucleosides that they are incorporated into the ____
viral DNA
adding acyclovir into the viral DNA strand, what happens?
acyclovir is missing the key group in adding the next nucleotide, the chain will be ended
acyclovir binds to the viral ___ complex to be added to the growing viral DNA strand
DNA polymerase
t/f acyclovir bind more strongly than endogenous nucletides so the DNA polymerase complex does not dissociate as easily
t
what is the significance of acyclovir binding to DNA polymerase?
inhibits progression of viral DNA synthesis and prevents the virus from replicating in the host cell
the mechanims of acyclovir and similar drugs is specific to the viral DNA replication process because the first step in creating the _____ is catalyzed by a viral enzyme, not a host enzyme
nucleotide monophosphate
t/f the host-made nucleotides will not contain acyclovir, only the viral ones
true
t/f HSV cannot be completely cleared from the host, but can be managed to an asymptomatic level
t
HSV infections are more easily transmited from ___- sores containing high # of viral particles
open
how can resistance to nucleoside analogues like acyclovir happen?
mutations of viral enzymes responsible for incorporating acyclovir into nucleotides ; mutations in DNA polymerase
ribavirin is a ____ analogue
nucleoside
Ribavrin gets incorporated into the ____ and impairs ___
viral synthetic pathways; viral RNA synthesis
ribavirn becomes a ___ nucleotide inside the cell
phosphorylated
interferon ___ has been shown to have benefit in patients with hepatitis C infections
alpha
interferons increase the activation of host ____ cells which recognize foreign bodies and infected host cells and destroy them
cytotoxic T
why are interferons not commonly used?
non-specific activation of immune system causes systemic effects
Maraviroc is an antiviral agent that blocks ____ receptors on the surface of host cells
CCR5
what is the purpose of Maraviroc binding to the CCR5 receptors on host cells?
prevents HIV from entering the host cell
t/f not all HIV strains bind to the CCR5 receptor, so Maraviroc does not always work
t
is Maraviroc approved in Canada for prophylactic HIV?
no
____ and ___ inhibitors can also be used to reduce the replication of HIV within host cells and release of viral particles
integrase and protease
___ is the key enzyme in the replication of HIV
reverse transcriptase
the ____ enzyme was one of the first targets addressed by HIV treatment
reverse transcriptase
there are 2 classes of reverse transcriptase inhibitors: ___ and ___
nucleoside type (NRTIs) and non-Nucleoside type (NNRTIs)
give an example of an NRTI
emtricitabine
give an example of an NNRTI
etravirine
what is Emtricitabine?
NRTI, nucleoside reverse transcriptase inhibitor
Emtricitabine is converted to ____ inside cells
triphosphate nucleotides
MOA of NRTIs
structurally similar to endogenous nucleosides and get incorporated into the HIV viral DNA, resulting in chain termination
emtricitabine has a similar MOA as ____
acyclovir
do NNRTIs resemble nucleosides?
no
NNRTIs are not structurally similar to nucleosides, but have high affinity for ____
HIV reverse transcriptase enzyme
MOA of Etavirine?
inhibits the enzymatic action of reverse transcriptase, preventing the production of HIV viral DNA in host cells
t/f reverse transcriptase inhibitors are usually given in combination with other anti-HIV agents to attack the virus from multiple aspects of replication
t
t/f in some situations, multiple reverse transcriptase inhibitors are used togther in attempt to counteract HIV mutations and resistance to single agenst
t
the yearly flu vaccine is based on predictions of ___
which strains will be the most problematic this year
what is neuraminidase?
one viral enzyme expressed by influenza that can be targetted
____ is the viral enzyme required to allow the newly synthesized influenza particles to be released from the host cell
neuraminidase
why is neuraminidase required for influenza to release viral particles?
our human cells dont bud or release little packages
give an example of a neuraminidase inhibitor
oseltamavir (tamiflu)
oseltamavir has been shown to be effective at reducing the severity of ____ and ____ infections if administered early
influenza A and B
ideally, oseltamivir needs to be taken within ___ hrs of exposure to influenza or within ___ hrs of onset of symptoms
48; 24
explain the replication process of COVID
virus enters cells by binding to angiotensin converting enzyme 2 (ACE) receptors, internalized, virla RNA is released from endosomes into the host cell cytoplasm where the viral genome is replicated and packaged into new particles for release and more infection
what re 2 drug currently being discussed wrt COVID?
remdesivir and hydroxychloroquine
what is remdesivir?
antiviral developed as potnetial treatmet for Ebolsa, now as potnetial for COVID
what is hydroxychloroquine?
antimalarial drug now considered for COVID
what type of antiviral is remdesivir?
nucleoside analogue
resdemavir has structural similarities to ___
adenosine
how does resdemavir work>
remdesivir nucleoside is processed during viral nucleotide biosynthesis ans is incorporated into the viral RNA, causing chain termination and preventing replication
is resdemavir approved in Canada for COVID?
yes, with several conditions , includin gwithdrawing approval if ADRs occur
hydroxychloroquine is used in some autoimmune diseases such as ___
Lupus
does hydroxychloroquine have scientific evidence to support its use in COVID?
no
t/f the antiviral actions of hydroxychloroquine are not as well understood as those of remdesivir
t
what is the proposed antiviral mechanism of hydroxychloroquine?
reduce viral endosome acidification, which prevents the viral components from being relased into the host cell cytoplasm
what are some of the ADRs of hydroxychloroquine?
irreversible blindness and possibly life-threatening arrhythmias, GI disturbances, neurologic effcets
what drug was Trump given for COVID?
REGN-COV2
what is an example of a neutralizing antibody used to treat COVID?
bamlanivimab
neutralizing antibodes used for COVD bind to the __
spike protein
MOA of neutralizing antibodies in treatment of COVID
binds to spike protein, prevents entry of the virus into the host cells, reduces ciral replication, and then has cell get recognized by immune system
protective immunity wears off over time and is ineffective when viruses ___
mutate
